The role of inflammation in the development of epilepsy

Abstract

Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with a history of previous lesions in the nervous system. Impaired regulation of the activation and resolution of inflammatory cells and molecules in the injured neuronal tissue is a critical factor to the development of epilepsy. However, it is still unclear as to how that unbalanced regulation of inflammation contributes to epilepsy. Therefore, one of the goals in epilepsy research is to identify and elucidate the interconnected inflammatory pathways in systemic and neurological disorders that may further develop epilepsy progression. In this paper, inflammatory molecules, in neurological and systemic disorders (rheumatoid arthritis, Crohn’s, Type I Diabetes, etc.) that could contribute to epilepsy development, are reviewed.Understanding the neurobiology of inflammation in epileptogenesis will contribute to the development of new biomarkers for better screening of patients at risk for epilepsy and new therapeutic targets for both prophylaxis and treatment of epilepsy.

Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

“…Generalized TSPO activation may be directly induced by the initial insult, while the sustained activation in specific regions suggests that microglial activation may have a role in epileptogenesis, as often proposed. 36,37 As part of the neuroinflammatory response, astrogliosis has been widely studied in epilepsy, including PET studies in epileptic patients. 38,39 However, to our knowledge, no PET studies targeting astrocytical activation in animal models of epileptogenesis have been published yet.…”

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

“…IL‐1β drives the pathologic role of brain inflammation in epilepsy . Studies on surgically resected epileptogenic foci from drug‐resistant forms of epilepsy with structural or infectious etiologies showed that the IL‐1α–IL‐1R1 axis is activated in neurons, glia, and endothelial cells of the BBB .…”

“…IL-1β drives the pathologic role of brain inflammation in epilepsy. [104][105][106][107][108][109][110][111][112] Studies on surgically resected epileptogenic foci from drug-resistant forms of epilepsy with structural or infectious etiologies showed that the IL-1α-IL-1R1 axis is activated in neurons, glia, and endothelial cells of the BBB. 104,107,[113][114][115] Similar findings were reported in animal models of acute symptomatic seizures, febrile and nonfebrile SE, and models of acquired epilepsies, 107,114 absence epilepsy, and progressive myoclonic epilepsy.…”

Postencephalitic epilepsy in dogs with meningoencephalitis of unknown origin: Clinical features, risk factors, and long‐term outcome

“…Epilepsy is a complex disease characterized by recurrent unprovoked epileptic seizures . Due to different underlying mechanisms as well as prognosis, it is important to distinguish acute symptomatic seizures (ASS) from late unprovoked seizures . ASS are events occurring in close temporal association with an acute or an active CNS insult, whereas unprovoked seizures occur in the absence of a triggering condition or beyond the interval estimated for the occurrence of ASS …”

“…5,6 Due to different underlying mechanisms as well as prognosis, it is important to distinguish acute symptomatic seizures (ASS) from late unprovoked seizures. 7,8 ASS are events occurring in close temporal association with an acute or an active CNS insult, whereas unprovoked seizures occur in the absence of a triggering condition or beyond the interval estimated for the occurrence of ASS. 9,10 In human medicine, the prevalence of postencephalitic epilepsy (PEE) varies between studies, ranging from 6.1% to 46.5% [11][12][13][14][15][16] and, a substantial number of patients are refractory to antiepileptic drug (AED) treatment.…”